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Intensive Glycemic Control Hazardous for Injured Brain

Intensive glycemic control is highly effective for treating sepsis, but it may be harmful for brain injury patients.

Studies indicate that intensive glycemic control can significantly reduce mortality in critically ill patients, but research from the University of California in Los Angeles (UCLA) suggests something else.

In a study of traumatic brain injury patients, intensive insulin treatment significantly reduced the level of glucose in the brain, Paul Vespa, MD, reported here at the 34th Critical Care Congress of the Society of Critical Care Medicine (SCCM). The reduction in extracellular glucose "did not affect the way the brain metabolized glucose."

Dr. Vespa said that "it is well known that early after trauma there is a large increase in glucose utilization followed by systemic hyperglycemia. Thus, there is fairly universal consensus that glycemic control will improve outcome." But he said the consensus is not based on brain monitoring, so little is known about the actual effect of glycemic control on brain functioning.

There are dramatic decreases in interstitial glucose levels associated with brain ischemia, and brain glucose is barely detectable at end of life, Dr. Vespa said. He and his colleagues used microdialysis to measure brain glucose and positron emission tomography (PET) to measure metabolism of glucose in the brains of traumatic brain injury patients undergoing continuous insulin infusion with a goal in the 90 to 120 mg/dL range.

"In 300 samples drawn from 50 patients, there was no relationship between serum glucose and PET-derived measure of whole brain glucose metabolism," Dr. Vespa said.

Fifteen patients with baseline hyperglycemia underwent cerebral microdialysis to assess brain glucose levels. In these patients, a 10% to 15% decline in serum glucose was associated with a mean 70% decline in cerebral microdialysis glucose "but no significant reduction in glucose metabolism."

Brain glucose reaches excessively low — and potentially dangerous — levels "about 30% of the time during infusion," Dr. Vespa said. Cerebral microdialysis glucose levels of 0.2 mmol/L or less "during intensive glucose control is an independent predictor of bad outcome in a traumatic brain injury patient."

In an interview, Dr. Vespa said that the findings suggest that brain injury patients should undergo brain monitoring during insulin infusion therapy.

Michael Diringer, MD, a professor of neurology, neurosurgery, and anesthesiology at Washington University School of Medicine in St. Louis, Missouri, stated that the UCLA team is "raising a red flag about the effect of intensive glycemic control, but they are using a fairly indirect measure to do so, especially since there was no change in the rate of the brains’ use of glucose."

Dr. Diringer, who moderated the SCCM abstract session during which Dr. Vespa presented his findings, added that intensive care unit "monitoring of brain tissue by microdialysis is difficult" and it is unlikely that routine monitoring can be initiated "without knowing what these numbers mean." For example, he said that "glucose levels are a good indictor at the extremes — the healthy brain and the dying brain — but we don’t have a real understanding of what the level means outside those extremes."
SCCM 34th Critical Care Congress: Abstract 76. Presented Jan. 18, 2005.

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